MSG and its negative health effects may have a bad rep, but it is important to have sufficient (not too much) glutamate. Glutamate is not only the most important neurotransmitter we have, but it also has important roles in the gut and immune system.

Read this post to learn more about eight important roles of glutamate and negative health effects of excess glutamate.

What is Glutamate?

The Role of Glutamate in the Body

Glutamate, also called glutamic acid, is one of the most abundant amino acids in the human body. The highest concentrations are present in the brain and muscles [12].

It also plays an important role in cell energy production and protein synthesis [13].

On the other hand, excessive levels lead to neurological and mental diseases [4].

Glutamate Vs. Glutamic Acid

Glutamate is interchangeable with glutamic acid, but it is chemically distinct from glutamine. The distinction is that glutamate has a hydroxyl (-OH) group, whereas glutamine has an ammonia (-NH3) group, as shown in the picture below. Read this post to learn more about glutamine.

Health Benefits of Glutamate

1) Helps the Brain Function

It is the most important neurotransmitter for normal brain function [5].

Nearly all excitatory neurons in the brain and spinal cord (central nervous system) are glutamatergic.

As the main excitatory neurotransmitter, it sends signals to the brain and throughout the body. It helps cognitive function, memory, learning, and other brain functions [6].

Glutamate is a non-essential amino acid that does not cross the blood-brain barrier and must be generated inside the brain cells locally from glutamine and other precursors [5].

However, glutamate in the blood may enter the brain if the blood-brain barrier is leaky [7].

Glutamate plays an important role in brain development [8].

The brain needs glutamate to form memories [9].

Low levels of glutamate cause problems in the brain. Increasing glutamate levels in the brain improve its functions.

Glutamate levels are lower in schizophrenic adults than healthy adults [10].

Low amounts of metabotropic glutamate receptor type 5 (mGluR5) indicate poor brain development in epilepsy patients [11].

Low glutamate release might cause autism spectrum disorder in mice [12].

Also, low levels are linked to major psychiatric disorders [13].

In rats, increasing leucine increases glutamate entry into the brain. This can increase and restore brain function after brain injury [14].

2) A Precursor for GABA

The body uses glutamate to produce neurotransmitter GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter that plays an important role in learning and muscle contraction [15]. In addition, GABA is known as a calming neurotransmitter that helps reduce anxiety and sleep.

The enzyme Glutamic Acid Decarboxylase (GAD) converts glutamate to GABA. Autoimmunity against GAD (also a marker for type 1 diabetes) results in too little GABA and too much glutamate.

3) Glutamate in Foods Improves Gut Function

Dietary glutamate is the main energy source for the gut cells and an important substrate for the synthesis of amino acids in the gut [16].

Food-derived glutamate triggers the digestive system and the entire body to respond to foods by [17]:

  • Activating the vagus nerve via nitric oxide and serotonin secretion in the gut
  • Stimulating gut movement by increasing gut serotonin levels
  • Increasing body heat and energy production in response to eating

It is also required for the production of antioxidant glutathione thus maintaining healthy gut lining [1819].

When given orally, a supplement of arginine and glutamate improves gut movement. In rats and dogs, the supplement treated gut dysfunction [20].

Glutamate protects the stomach lining from H. pylori and non-steroidal anti-inflammatory drugs [2122].

4) Glutamate in Foods Increases Appetite and Satiety

The presence of glutamate in foods might also signal to our bodies that we are getting high-protein foods, which our bodies prefer.

The presence of MSG in foods increases appetite as we eat, but also increases satiety after we consume the foods [23].

5) Blood Glutamate Plays a Role in Immunity

Glutamate receptors are present on immune cells (T cells, B cells, macrophages, and dendritic cells), which suggest a role of glutamate both in the innate and adaptive immune systems [24].

Glutamate has very potent effects not only on normal but also on cancer and autoimmune pathological T cells. Therefore, glutamate and drugs that activate glutamate receptors might be used in the treatment of cancer and infectious organisms [25].

Glutamate increases regulatory T cells (Treg) and may have a protective role in inflammatory neurodegenerative diseases [26, 27].

B-cells produced more IgG and IgE when cultured with glutamate [28].

6) Cellular Glutamate Increases Longevity

In yeasts, increasing glutamate levels slow down cellular aging and increases lifespan [29, 30].

In chickens, a supplement of glutamine and glutamic acid reduced mortality rates compared to ones with normal diets [31].

7) Associated with Bone Health

Glutamate is important for the growth and development of the bone [24].

It decreases the development of cells that degrade bones (osteoclasts) and may aid in the treatment of a variety of bone diseases, such as osteoporosis in humans [32].

8) Important for Muscle Function

Glutamate may play an important role in muscle function [33].

During exercise, glutamate plays a central role in providing energy and glutathione production [34].

Glutamate may promote the development of muscular dystrophy in animal models [35].

Negative Effects of Glutamate

1) Excess Glutamate Causes Neurological Disorders

Excess glutamate in the brain may be a risk factor for brain disease and cognitive impairments [3637].

In mice, higher levels cause abnormal movements due to brain motor function control [38].

Traumatic Brain Injuries

After a patient suffers from a stroke or traumatic brain injury, excess glutamate levels contribute to brain damage [4].

In traumatic brain injuries, leaky blood-brain barrier allows glutamate in the blood to enter the brain [7].

Epilepsy

Excess levels of the glutamate receptor mGluR5 can cause epilepsy. In rats, Pu-erh tea decreases mGluR5 and may be a natural neuroprotective agent by relieving epilepsy in rats [39].

In mice, blocking mGlu5 (a Glu receptor) also helps relieve the effects of chronic stress [40].

Increased glutamate concentration may contribute to lipopolysaccharide-induced seizure development [41].

Depression

Changes in glutamate energy production are associated with depression and suicide. Major depressive disorder patients have higher Glu levels [42].

Multiple Sclerosis

It may also cause multiple sclerosis, a condition where nerve cells do not function properly [4344].

ALS

Glutamate accumulation damages nerve cells and may lead to the progressive, debilitating disease amyotrophic lateral sclerosis (ALS) [4546].

Alzheimer’s and Neurodegenerative Diseases

Also, disturbances in glutamate transmission in the brain have been linked with loss of memory and learning ability in Alzheimer’s disease patients [474849].

Excess inflammatory cytokine TNF can cause glutamate toxicity. Blocking TNF treats neurodegenerative diseases by preventing high glutamate levels [50].

2) Might Increase Cancer-Related Problems

In animal models, blocking the ionotropic glutamate receptor (iGluRs) can be a potential cancer treatment [51].

Additionally, high levels of glutamate heighten levels of cancer-induced bone pain [52].

3) Glutamate Receptors Contribute to Pain

Glutamate receptors and glutamatergic synapses transmit pain and itch sensation. They also contribute to chronic pain. Decreasing the glutamatergic pathway helps reduce pain [53].

4) May Cause Diabetes

Long-term high glutamate levels may contribute to diabetes development in both type 1 and type 2 diabetes [5455].

Excess glutamate may accelerate the damage of pancreatic cells that secrete insulin [545556].

5) Excess Glutamate May Cause Migraine

Migraines are a neurovascular disorder accompanied by severe headaches and neurological symptoms.

Many migraine patients react to monosodium glutamate added to foods [57].

Blood glutamate levels correlate with the severity of symptoms in migraine patients [58].

Glutamate may be involved in transmitting pain signals to the brain and trigeminal nerves of migraine patients [59].

Several drugs that block glutamate receptors are showing some positive results in clinical trials for the treatment of migraines [57].

Sources & Sensitivities

Sources

Glutamate is naturally made by the body (non-essential amino acid) and found in food sources and supplements [1].

Food sources of glutamate include protein-rich food such as meat, poultry, eggs, tomatoes, cheese, mushrooms, and soy [60].

Glutamate gives its food “umami” taste, the fifth basic taste, along with sweetness, saltiness, sourness, and bitterness [2].

MSG (monosodium glutamate), a common flavor and taste enhancer in food, is a significant source of glutamate [60].

Breast milk has the highest concentration of glutamate among all amino acids. Glutamate makes up more than 50 percent of amino acids in breast milk [61].

People normally do not need to take supplements because sufficient levels of glutamate are available in the body and normal diets [4].

Glutamate supplements are beneficial for people who are deficient in protein, but they should not be used by people with neurological, kidney, or liver diseases.

Sensitivities

The Joint FAO and WHO Expert Committee on Food Additives (JECFA) concluded that glutamate as an additive in food is not a health hazard to humans [62].

However, some individuals may exhibit allergic reactions such as a burning sensation, headache, nausea, and chest pains when exposed to glutamate. People sensitive to glutamate should avoid the use of it [63].

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